Differential regulation of hypoxanthine and xanthine by obesity in a general population.

Uric acid is synthesized by oxidation of hypoxanthine and xanthine using a catalyzing enzyme, xanthine oxidoreductase (XOR), which can be a source of reactive oxygen species. Plasma XOR activity is a metabolic biomarker associated with obesity, hyperuricemia, liver dysfunction and insulin resistance. However, it has recently been reported that XOR activity in fat tissue is low in humans unlike in rodents and that hypoxanthine is secreted from human fat tissue.The associations of obesity with hypoxanthine, xanthine and plasma XOR activity were investigated in 484 subjects (male/female: 224/260) of the Tanno-Sobetsu Study.Levels of hypoxanthine, xanthine and plasma XOR activity were significantly higher in males than in females. In 59 subjects with hyperuricemia, 11 (male/female: 11/0) subjects were being treated with an XOR inhibitor and had a significantly higher level of xanthine, but not hypoxanthine, than that in subjects without treatment. In all of the subjects, hypoxanthine concentration in smokers was significantly higher than that in non-smokers. Stepwise and multivariate regression analyses demonstrated that body mass index, smoking habit and xanthine were independent predictors of hypoxanthine after adjustment of age, sex and use of antihyperuricemic drugs. Whereas, alanine transaminase, hypoxanthine and plasma XOR activity were independent predictors for xanthine, and alanine transaminase, triglycerides and xanthine were independent predictors for plasma XOR activity.The concentration of hypoxanthine, but not that of xanthine, is independently associated with obesity and smoking habit, indicating differential regulation of hypoxanthine and xanthine in a general population.